Uremic pruritus is a disorder associated with chronic kidney disease. Pruritus, or itch, is a sensation that stimulates the desire or reflex to scratch, which can be either generalized or localized. The cause of uremic pruritus is not fully understood. Overactivity of type 1 T helper cells (TH1) has been demonstrated in uremic pruritus. Furthermore, serum levels of interleukin-2, a cytokine produced by TH1 cells, have been demonstrated to be higher in dialysis patients with itch compared to dialysis patients without itch. This cytokine has a well-documented role in induction of pruritus (Fallahzadeh et al., Nephrol. Dial. Transplant. (2011) 26 (10): 3338-3344). Other proposed contributors to the pathogenesis of uremic pruritus may include anemia or other manifestation of erythropoietin deficiency, inadequate dialysis, histamine release from skin mast cells, skin dryness, secondary hyperparathyroidism, hyperphosphatemia with increased calcium phosphate deposition in the skin and alterations in the endogenous opioidergic system with overexpression of opioid receptors.
Uremic pruritus in patients with kidney failure and/or among patients undergoing dialysis can be quite disabling. For example, chronic uremic pruritus leads to a statistically significant deleterious impact on the patient that can be scientifically measured in the realms of Quality of Life impairment, sleep disruption problems, social functioning and affective disturbances (Mathur et al., Clin J Am Soc Nephrol. 2010; Pisoni et al., Nephrol Dial Transplant 2006 (21): 3495-3505, and references therein). In addition to increased morbidity, Pisoni et al. and Narita et al. (Kidney Int 2006 (69) 1626-1632) have also demonstrated that this patient population has increased mortality, and that such increased mortality can be reasonably attributed to the failure to adequately treat the pruritus. Despite advances in the care of patients with kidney disease and end-stage renal disease (ESRD) patients, the treatment and management of uremic pruritus remains a challenge. Accordingly, there is a need for effective methods to treat uremic pruritus.